Field of the Invention
The present invention relates to high intensity focused ultrasound (HIFU), and a system for treatment using HIFU.
Description of the Related Art
Ultrasound
Sound waves are mechanical waves, typically generated by vibration, that propagate in a transmission medium such as air, water or human tissue. A sound wave may be categorized as follows based on its frequency:                a sound wave less than the lower limit of human hearing, typically 16 Hz, is called an infrasonic wave or infrasound;        a sound wave within the range of human hearing, typically from 16 Hz to 20 KHz, is called an acoustic wave; and        a sound wave greater than the upper limit of human hearing, typically greater than 20 KHz, is called an ultrasonic wave or ultrasound;        
Ultrasonic waves can transmit higher energy than acoustic waves. For example: a 1 MHz ultrasonic wave of the same amplitude as a 1 KHz acoustic wave transmits 100 times the energy. Ultrasound is ideal for applications requiring the transmission of large amounts of energy, though are often used in low energy applications as well.
In most systems, ultrasonic waves are generated by a piezoelectric material converting electrical energy to mechanical vibration and vice-versa. When vibration is induced on a piezoelectric material, an alternating voltage is produced between two surfaces of this material. This is the piezoelectric effect. Conversely, when alternating voltage is applied between two surfaces of this material, the material will vibrate with the same frequency as the alternating voltage being applied. This is called the inverse piezoelectric effect. A common piezoelectric material is quartz crystal, but there are many other piezoelectric materials. Typically, the piezoelectric elements that generate or receive ultrasonic energy are called transducers.
In some designs, an alternating current electric signal is applied to the opposite sides of the transducer. During the positive phase of the alternating voltage, the transducer is compressed, and during the negative phase of the alternating voltage, the transducer is stretched. When alternating electric signal is applied to the transducer surfaces, the transducer makes macroscopic deformations. The frequency of the vibrations is dictated by and matches the frequency of the alternating voltage signal. This movement produces ultrasound waves with the desired frequency.
Piezoelectric materials of different thickness or compositions may have different inherent resonance frequencies. When the frequency of an alternating electric signal matches the inherent resonance frequency of a transducer, the amplitude of vibration is greatest.
The distance that an ultrasonic wave transmits within one second is called the ultrasonic wave propagation velocity, or sound velocity. The ultrasonic sound velocity is different in different kinds of matter; and will change with changes in temperature, pressure and other factors.
When an ultrasonic wave is transmitted in the elastic medium, besides the pressure received when the system is at rest, the particles in the medium receive additional pressure p, alternating with time. We call the latter sound pressure, usually expressed in pascals. For a plain sound wave, it can be proved by the principle of acoustics that the amount of sound pressure may be expressed as:p=ρcωA 
In the equation, ρ is the mass density of the medium, ωA is the range of vibration velocity of the particle, c is the sound velocity. Since ρc is typically a physical constant of the sound medium, it is usually called the specific impedance of the medium, or simply the sound impedance, Z. The unit of Z is rayls.1 rayls=1 g/cm2s
While discussing sound transmission, sound impedance is an extremely important physical quantity. If the Z value of the medium is constant throughout the medium in the direction of travel of the sound wave, the sound wave will not change its direction when transmitted in the medium, and will transmit forward constantly. In contrast, if the Z value of the medium is non-uniform, so-called acoustics interference will be shown at the variation position. According to terminology in acoustics interference, the sound wave will be reflected, refracted or scattered.
While the ultrasonic wave propagates in an elastic medium, the wave's energy attenuates. There are three typical causes of attenuation:                energy losses due to expansion of the wave front,        energy losses due to scattering, and        energy losses due to absorption in the medium.        
The ultrasonic wave starts with a finite amount of energy. As the ultrasonic wave spreads, that energy is distributed over a larger wave front, weakening the effect of the wave at any given point. Focusing the ultrasound, as discussed below, can have the opposite effect in the focal region.
During the course of transmission of the ultrasonic wave, if it meets the acoustic impedance and a changing interface whose dimension is equal or smaller than the wavelength, a situation different from reflection will happen. A part of the acoustic energy is dispersed to all directions (“scattering”); the remaining acoustic energy continues spreading forward.
In common tap water, bubble and impurities in the water can cause scattering and make the ultrasonic energy attenuated. Therefore, de-aerated water is used in the ultrasonic treatment in order to reduce the scattering, so that more ultrasonic energy can reach the desired focus position. Similarly, the human body is made up of mediums (skin, fat, etc. . . . ) with different sound impedances, so as the sound wave travels through different tissue, some scattering will occur, which causes the wave energy to attenuate.
While the ultrasonic wave is transmitted in the tissue, its energy will also be absorbed constantly by the tissue as the wave propagates. There are at least a few principal mechanisms involved:                Viscous absorption: When the ultrasonic wave is transmitted in the tissue, vibration particles will have to overcome the viscous resistance of the particle, losing some energy in the process.        Heat conduction absorption: In the course of the transmission of sound waves, the positive and negative sound pressure in the medium will create cyclic diffusion. The temperature in positive sound pressure will rise, in negative sound pressure, the pressure will diffuse. Internal heat conduction will cause heat loss, consuming sound energy.        Molecular relaxation absorption: This is due to internal dynamics within the molecule of the medium. For instance, redistribution of the energy internal and external to the molecule, molecular structure change and chemical change, etc., can cause sound energy consumption.        
The ultrasonic energy that the medium absorbs turns into heat energy, which increases the temperature. The sound intensity of the propagating wave decreases predictably as the propagation distance increases.
Current ultrasonic diagnosis imagery technology (such as b-scan diagnostic ultrasound) has been established on the foundation of the ultrasonic reflections and refractions (ultrasonic echo) from the human body. Its foundation is based on the fact that the acoustic impedance value of tissue is not uniform. Typically, when an organism suffers pathological change, its acoustic impedance value of the affected tissue changes, or the tissue itself move or changes shape, thus causing a corresponding change in the received ultrasonic echo. The ultrasonic echo thereby provides diagnostic information about pathological changes in a patient's tissue.
Ultrasonic Treatment
Over time, a number of methods to treat tissue with ultrasound have emerged. In the seventies, clinical physicians found that tumor cells are more sensitive to temperature than normal cells. Tumor cells die in abundance when their temperature is above 45 degrees Celsius. This early method of treatment irradiated the target region with a high-power ultrasonic wave while controlling the temperature at about 42 to 45 degrees Celsius accurately, through tissue temperature detection. With this early method, through electron focusing (or phased array focusing), the volume and shape of the target position is detected. All kinds of shapes can be regulated through electron focusing. This early method killed the tumor cells through long exposure (irradiation). Several systems of this design were developed in the last century.
Earlier systems had a number of drawbacks. Some of these earlier systems would take an unacceptably long time to treat the target tissue, which may require the patient to be sedated or otherwise immobilized to keep the target tissue still for the long periods of time required for treatment. Some of these earlier systems would require many hours of treatment to treat a large sized tissue mass.
Some early systems employing a phased array would generate harmonics that may create focused ultrasound outside of the focal point. A secondary harmonic may appear and damage tissue that is not an intended part of the treatment. Phased arrays also may have quality control and cost issues related to producing a completely consistent set of transducer elements. Minor variances in the characteristics of the transducer elements may produce ultrasound that is outside an acceptable range by hundreds or even thousands of Hz. Each transducer element has to be thoroughly checked for quality control, adding significantly to the cost of such a system. In addition, these minor variances between transducer elements may lead to difficulties in getting all the transducers in the array to fire simultaneously, to ensure that the resulting waves are properly in phase. Minor variances may cause the waves to be out of phase, degrading the performance of the phased array.
Researchers began to study the treatment of malignant tumors using heat at higher temperatures and more intense ultrasound, which lead to the development of a second method of ablating tissue using ultrasound therapy technology: HIFU technology.
In the 90's, HIFU research work started around the world. The HIFU treatment method generally involve generating an ultrasonic wave some distance away from the focal region, sometimes outside the patient's body, and focusing the HIFU energy (often measuring greater than one thousand watts per square centimeter (“W/cm2”)) at the target tissue inside the body, heating the target tissue rapidly to approximately 70 degrees Celsius or greater. The rapidly heated target tissue is ablated and destroyed, removing the threat that the target tissue may have posed.
High Intensity Focused Ultrasound
High Intensity Focused Ultrasound (HIFU) is one of the emerging medical treatment methods. HIFU is ultrasound in the range of approximately 0.2 MHz to 3.5 MHz, generated and focused to produce very high intensity sound at the focal point. The intensity of sound at the focal point can range from 500 W/cm2 to upwards of 50 kW/cm2.
During HIFU treatment, ultrasonic waves mainly produce the following four effects to tissue:                Heat effect: when ultrasound acts on tissue, it generates heat in the focal region. The tissue absorbs ultrasonic energy and converts it to heat, and in addition heat is generated by the reflection of ultrasonic waves on different surrounding tissues back on the target tissue. The heat effect is a basic mechanism of a HIFU treatment system. Temperatures in the focal region typically exceed 70° C.        Cavitation effect: under alternating sound pressure, the moisture in the target tissue cells in the focal region form tiny gas filled cavities or bubbles. Under high vibration intensity, the bubbles may explode, producing a shock wave that may cause a series of biochemical reactions and mechanical effects which in turn cause the destruction of the target cells.        Mechanical effect: the ultrasound mechanical vibrates the target tissue, which may affect the functional physiological processes and the whole structure of the cells in the acoustic field.        Immunoreaction: Research indicates that ultrasonic treatment to a tumor, can induce the immune response of the target tissue and weaken the tumor cells indirectly.        
The target tissue may be a tumor or growth, fat cells, or any other type of biological matter within the body. Depending on the type of tissue and the desired effect, HIFU may be used to cut off blood flow to the target tissue, or destroy it altogether.
By using a therapeutic transducer, such as HIFU transducer shaped, or adapted with a lens, to direct the sound, the ultrasound beam may be concentrated on a focal region, resulting in maximum acoustical pressure concentrated in this region. A therapeutic transducer may also include a plurality of transducers elements all focused on the focal point, producing HIFU.
Tissue heating, cavitation, and the other effects are directly related to the acoustical pressure level. The highest level of acoustical pressure is in the focal region, and thus the consequent effects are most concentrated there. Due to these effects, a necrotic lesion is formed in the target tissue where the focal region lies.
In order for the HIFU system to work well, there are a number of considerations related to the treatment of tissue that need to be addressed.
The treatment method should kill the unwanted tissue without overly damaging the normal tissue around it.
The HIFU system should be able to change the location of the focal region, so that different types of treatments can be performed depending on where and what tissue is to be ablated. There is a need for a system that can minutely change the depth of the focal region. The depth is the distance of the focal region relative to the therapeutic head.
The HIFU system should be able to change to the angle at which it ablates tissue. Typically, the focal region defines volume of a known size and shape. The size and shape are determined by the characteristics of the HIFU transducer element. It is desirable to be able to manipulate the location of this volume in as many ways as practically possible, to minimize the risk of damage to normal tissue.
The HIFU system should be able to confirm the position and shape of the target tissue accurately. It is very important that the HIFU system targets and ablates only the target tissue, and not other tissue. The HIFU system, through computer and human oversight, should confirm the location and volume of the target tissue prior to treatment beginning on the body.
The HIFU system should be able to offer monitoring during treatment. The target tissue is not always fixed in place. The patient may move, or the treated tissue may shift the remaining target tissue during treatment. Also, the target tissue may require more treatment than originally scheduled in particular areas, and be instructed to do so as treatment progresses. Finally, it is important for safety reasons to confirm that the HIFU is focused precisely where it is supposed to be at all times.
Ultrasonic energy will attenuate while transmitting in tissue, due to heat losses and other effects. For this reason, treatment of target tissue located deep in the body requires that the HIFU system be able to generate high energy ultrasonic waves from the transducer, yet at the same time, it requires that the HIFU transducer focus the ultrasonic wave to a small focal region.
Some prior art systems use imaging systems, such as MRI or B-scan ultrasound, to confirm the position or shape of the target tissue before treatment. A few can monitor the treatment progress during treatment. U.S. Pat. No. 5,769,790 (“Watkins”) discloses one way to monitor the treatment progress using an imaging transducer, such as a B-scan ultrasound, in a fixed position relative to the therapeutic head. Other prior art, such as U.S. Pat. No. 6,685,639 (“Wang”) has the imaging transducer fixed beside or within the HIFU transducer to make up a therapeutic head. In each case, the imaging transducer is in a fixed position relative to the HIFU transducer, and focused where the focal region of the HIFU transducer is to be.
The problem with this approach is that the imaging transducer, typically B-scan ultrasound, being fixed relative to the HIFU transducer, is limited by its range of motion in what it can perceive before and during treatment. The B-scan ultrasound element images only a two dimensional plane, which does not reveal sufficient information about three dimensional structures in the body when fixed.
Operators of conventional handheld B-scan ultrasound units typically twist or rotate the handheld B-scan to get a sense of the topography of structures within the body. The rotation of a two dimensional scan can allow the operator to choose the most revealing two dimensional image, and gather information about the overall three dimensional structure.
Similarly, it is desirable to be able to vary the depth of the scan, so that the image produced shows detail about structures deeper within the body. On some patients, thick layers of fat or other tissue may obscure the target area. Operators of conventional handheld B-scan ultrasound units typically have to push the handheld B-scan into the body to get clear images of the structures deep within the body.
A system having the imaging transducer fixed to or incorporated into the HIFU element would have to rotate and push the entire head against the patient's body to capture clear images of some structures within the body, creating considerable discomfort. The HIFU element is typically a rigid element of considerable diameter, and pushing it against the patient's body is clearly undesirable.
Having an elongated imaging transducer that protrudes considerably into the field generated by the HIFU element may also be undesirable, as the imaging transducer may interfere with the transmission of the HIFU, and distort or degrade the strength and accuracy of the device.
The HIFU system should transmit the ultrasonic energy from the HIFU transducer into the body to the target tissue. Since it is well known that air is a relatively poor conductor for sound, deairated water is often used instead to propagate the sound from the HIFU transducer to the surface of the body with minimal and predictable energy losses. Any liquid with known sound transfer characteristics could be used, but deairated water is generally preferred, as its sound transfer characteristics are quite similar to that of living tissue. It is important that the HIFU system maintain water contact between the HIFU transducer and the body to prevent losses.
Some prior art systems use a bag to hold the deairated water and transmit the HIFU. This can be undesirable because a boundary layer of other material, such as the bag material, is placed either between the water and the body, or the HIFU transducer and the water, and scattering, diffraction, and heat losses occur at this boundary layer.
Some of the prior art uses an open ended bag, filled with deairated water, attached to the therapeutic head of the system. When the therapeutic head moves, it changes the volume enclosed by the open ended bag, and water is displaced out of the top of the bag. These changes in volume may lead to an air gap appearing between the body and the water, which would reduce the effectiveness of such a design.
It is necessary to have a system that prevents the appearance of such an air gap, without a boundary layer, and maintains direct contact between the deairated water and the body.
Many systems advocate either steady or pulsed HIFU in different patterns. Sustained HIFU of any significant duration may cause some discomfort or pain in patients, as the heating triggers nerve endings in the body to fire. It is desirable to have a method that minimizes discomfort from the heating.
There is a need to provide a HIFU system such as to remove or minimize the disadvantages mentioned above.